P935: REAL WORLD COMPARATIVE ANALYSIS OF THE EFFICACY OF TECLISTAMAB VERSUS CURRENT TREATMENTS IN PATIENTS WITH TRIPLE-CLASS EXPOSED RELAPSED/REFRACTORY MULTIPLE MYELOMA FROM THE LOCOMOTION STUDY
Authors: H. Einsele, P. Moreau, M. Delforge, N. W. van de Donk, F. Ghilotti, J. Diels, A. Elsada, V. Strulev, L. Pei, R. Kobos, J. Smit, M. Slavcev, K. Weisel, M.-V. Mateos
Journal: HemaSphere (2022)

Background: Patients with triple-class exposed relapsed/refractory multiple myeloma (TCE RRMM) have poor prognosis and limited treatment options after being treated with ≥3 lines of therapy (LOT). Teclistamab (tec), a B-cell maturation antigen × CD3 bispecific antibody, is currently being evaluated in the MajesTEC-1 (NCT04557098) study. MajesTEC-1 is a single-arm, phase 1/2 study in patients with TCE RRMM, previously exposed to an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody and received ≥3 LOT. Aims: Since MajesTEC-1 lacks a control arm, we performed a real-world comparative analysis of the efficacy of tec vs currently used treatments in clinical practice by creating an external real-world control arm from LocoMMotion (NCT04035226), a prospective study of real-world clinical practice (RWCP) efficacy and safety outcomes in patients with TCE RRMM who received ≥3 LOT. Methods: Patients from LocoMMotion (248 patients, clinical cutoff May 21, 2021) who met MajesTEC-1 eligibility criteria were used to create the external control arm for MajesTEC-1. Individual patient-level data were included for 150 patients from MajesTEC-1 treated with tec (1.5 mg/kg weekly) at a clinical cutoff of Sep 7, 2021. Inverse probability of treatment weighting with average treatment effect on the treated was used to adjust for imbalances in prognostically significant baseline covariates: Eastern Cooperative Oncology Group performance status, gender, type of MM, prior transplant, refractory status, International Staging System stage, time to progression on prior LOT, extramedullary disease, number of prior LOT, time since diagnosis, average duration of prior LOT, age, hemoglobin, lactate dehydrogenase and creatinine clearance. Efficacy of tec vs RWCP was measured for overall response rate (ORR), very good partial response (VGPR) rate, complete response or better (≥CR) rate, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Odds ratio, transformed into a response-rate ratio (RR) (along with 95% confidence interval [CI]), derived from weighted logistic regression was used for binary endpoints (ORR, VGPR rate, and ≥CR rate). Hazard ratios (HRs) and 95% CIs for time-to-event endpoints (DOR, PFS, and OS) were computed using a weighted Cox proportional hazards model. Results: After reweighting the external RWCP cohort, the 2 cohorts had well balanced baseline characteristics. Patients treated with tec had improved outcomes vs current treatments used in RWCP: ORR (RR: 2.31; 95% CI 1.75–2.87; P<0.0001), VGPR rate (RR: 5.54; 95% CI 3.38–7.70; P<0.0001), ≥CR rate (RR 91.50; 95% CI 12.66–661.43; P<0.0001), DOR (HR 0.17; 95% CI 0.08–0.36; P<0.0001), PFS (HR 0.47; 95% CI 0.34–0.67; P<0.0001), and OS (HR 0.69; 95% CI 0.46–1.05; P=0.08). Summary/Conclusion: In this analysis, significantly improved efficacy for almost all outcomes was observed with tec when compared with RWCP. This highlights the potential of tec as a highly effective treatment option for patients with TCE RRMM who have been exposed to ≥3 LOT.